Quantitative cytochemical detection of malignant and potentially malignant cells in the colon

It was found to be possible to distinguish malignant cells from normal cells by using an oxygen-sensitive tetrazolium salt (neotetrazolium) for the histochemical demonstration of glucose-6-phosphate dehydrogenase activity in cryostat sections of human colon. We have studied 12 cases of established adenocarcinoma of the colon in addition to 4 of ulcerative colitis and 4 of adenomatous polyposis (polyposis coli). In a nitrogen atmosphere the activities of malignant and normal cells were similar. However, after incubation in an atmosphere of pure oxygen, only malignant cells gave a positive reaction after 5 min. Three of the four cases of adenomatous polyposis gave a positive reaction for glucose-6-phosphate dehydrogenase activity in oxygen in a manner similar to that of specimens with severe dysplasia. In general, positive foci were histologically indistinguishable from the neighboring tubuli. However, foci of severely dysplastic epithelium usually showed a positive reaction. All three patients eventually developed clear-cut severe dysplasia. The other patient, who showed a negative reaction in oxygen, was diagnosed after 3 years as not suffering from dysplasia. All cases of ulcerative colitis gave a reaction in oxygen comparable with that of normal cells. Therefore, the areas with a positive reaction are considered to be either in the process of malignant transformation or malignant. An explanation for the oxygen insensitivity of cancer cells appeared to be a decrease in the activity of superoxide dismutase (EC 1.15.1.1), as addition of exogenous superoxide dismutase to malignant cells caused a normal reaction. We wish to suggest that this test in combination with the routine histology may be exploited for the diagnosis of polyps in premalignant conditions.